Thalidomide treatment ameliorates hepatopulmonary syndrome in rats with biliary cirrhosis

Abstract

Abstract: Objective To investigate the mechanism of thalidomide in the treatment of hepatopulmonary syndrome (HPS). Methods Common bile duct ligation was used to induce HPS in rats. Four weeks after operation, experimental group was treated by thalidomide [100 mg/(kg·d)], control group was treated by distilled water [100 mg/(kg·d)] for 2 weeks. Biochemical, plasma and bronchoalveolar lavage fluid vascular endothelial growth factor (VEGF), TNF-α and blood gas analysis were performed in all rats. The rat liver was collected for histopathological examination, and the lung tissue was analyzed by real-time fluorescence quantitative PCR and western blot. In another parallel group, the results showed that the model was successful. Results After thalidomide treatment, the alveolar-arterial partial pressure of oxygen (A-aPO₂) and the levels of serum VEGF and TNF-α were significantly decreased [A-aPO₂ rank was 25.10 (10) in thalidomide group, 15.60 (10) in control group (P<0.001), 25.50 (10) in thalidomide group, 14.50 (10) in control group (P<0.001). serum TNF-α level was 25.50 (10) in thalidomide treatment group, and 12.60 (10) in control group (P<0.001)]. Meanwhile, thalidomide decreased lung VEGF, VEGF receptor 2 (VEGFR-2) mRNA [(VEGF model group vs. thalidomide group: 23.25 (10) vs. 15.10 (10); VEGFR-2 model group vs. thalidomide group: 22.40 (10) vs. 15.60 (10)] and protein [VEGF model group vs. thalidomide thalidomide group: 2.03±0.96 vs. 1.45±0.99; VEGFR-2 model group vs. thalidomide group: 21.50 (10) vs. 12.25 (10)] expression (all P<0.05). Conclusion Thalidomide can reduce Amura PO₂ in choledochal ligation rats, suggesting that thalidomide can improve the HPS of experimental animal model. The mechanism may be related to the inhibition of TNF-α, to inhibit VEGF/VEGFR-2 pathway and reduce pulmonary angiogenesis.

Key words: Thalidomide, Hepatopulmonary syndrome, Biliary cirrhosis, Vascular endothelial growth factor, Tumor necrosis factor

JIANG Li-ping, JIANG Xiao-yan, WANG Hong-yan, WU Wen-jie, OU Yang, CHEN Ming-sheng. Thalidomide treatment ameliorates hepatopulmonary syndrome in rats with biliary cirrhosis[J]. Chinese Hepatolgy, 2023, 28(2): 175-180.

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